Beyond symptom reduction: Intranasal esketamine is associated with improved quality of life in treatment-resistant depression.

Objective: Treatment-resistant depression (TRD) is associated with severe functional impairment, poor quality of life, and increased suicide risk. This study evaluated the effectiveness of intranasal esketamine on depressive symptoms, hopelessness, suicidal ideation, and quality of life in patients with TRD, exploring whether outcomes differed according to concomitant antidepressant class (SSRI vs. SNRI).

Methods: Thirty-five outpatients with TRD received intranasal esketamine combined with an oral antidepressant. Assessments were conducted at baseline, 3 months, and 6 months using the Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory-II (BDI-II), Beck Hopelessness Scale (BHS), Columbia-Suicide Severity Rating Scale (C-SSRS), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Mixed Models for Repeated Measures and Generalized Estimating Equations were applied.

Results: Significant improvements over time were observed in depressive symptoms, hopelessness, and quality of life as measured by the Q-LES-Q (all p < .001). Suicidal ideation significantly decreased during follow-up (p = .025). Improvement in Q-LES-Q scores exceeded the threshold for clinical meaningfulness. No significant differences emerged between SSRI and SNRI subgroups across outcome measures.

Conclusions: Intranasal esketamine was associated with significant improvements in depressive symptoms, hopelessness, suicidal ideation, and quality of life over 6 months in patients with TRD, with no statistically significant differences detected across antidepressant subgroups in this exploratory comparison.